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BK Polyomavirus microRNA in Kidney Transplant Recipient
Rajat Nog1, Brahmaraju Mopidevi2, Indu Sivankutty2
1Department of Medicine, Westchester Medical Center, Valhalla, NY.
Abstract:
BK polyomavirus-associated nephropathy (PyVAN) remains a serious threat for renal dysfunction and graft loss in kidney transplant recipients on immunosuppressive medication. In this study, a pilot cohort of 16 kidney transplant recipients were recruited of which eight were with significant BKPV viremia (sBKPV) and the rest were controls matched to age, gender, and time since transplant. We used next-generation sequencing to characterize the miRNA expression profile in urine samples. In total, the expression of 8 miRNAs (miR-16-5p,miR-200c-3p,bkv-miR-B1-3p,let-7b-3p,miR-1269b,bkv-miR-B1-5p,miR-193a-3p,miR-944) were upregulated whereas 21miRNAs (miR-134-5p,miR-4724-5p,miR-127-3p,miR-6500-3p,miR-507,miR-378b,miR-3911,miR-211-5p,miR-486-5p,miR-143-3p,miR-3195,miR-1307-5p,miR-29a-5p,miR-378f,miR-12136,miR-378g,miR-144-3p,miR-378a-3p,let-7i-5p,miR-204-5p,miR-146a-5p) were downregulated with fold change > 2. We found that bkv-miR-B1-5p and bkv-miR-B1-3p have 19-fold and 5-fold higher expression values in BKPV viremia patient samples, respectively. A few earlier studies have reported BKV miRNA in urine and serum samples using the RT- PCR from PyVAN patients. Our results corroborated findings from earlier studies and highlighted the need for additional evaluation of the role of sequencing approaches for monitoring BKPV specific and host miRNAs to better understand the viral reactivation and disease pathogenesis.
Insights
BK polyomavirus (BKPV) infection poses a risk to kidney transplant recipients. Next-generation sequencing identified distinct miRNA profiles in urine, with BKPV-specific miRNAs significantly upregulated in viremic patients, aiding in understanding disease pathogenesis.
Area of Science:
- Nephrology
- Virology
- Molecular Biology
Background:
- BK polyomavirus-associated nephropathy (PyVAN) is a significant cause of kidney transplant dysfunction and graft loss.
- Immunosuppressive therapy post-transplant increases the risk of BKPV reactivation and viremia.
Purpose of the Study:
- To characterize the urinary microRNA (miRNA) expression profile in kidney transplant recipients with BKPV viremia.
- To identify potential miRNA biomarkers for monitoring BKPV infection and disease progression.
Main Methods:
- Pilot study involving 16 kidney transplant recipients (8 with significant BKPV viremia, 8 controls).
- Next-generation sequencing was employed to analyze miRNA expression in urine samples.
- Differential expression analysis was performed with a fold change threshold of > 2.
Main Results:
- Significant differential expression of 8 upregulated and 21 downregulated miRNAs was observed in patients with BKPV viremia.
- BKPV-specific miRNAs, bkv-miR-B1-5p and bkv-miR-B1-3p, showed markedly higher expression (19-fold and 5-fold, respectively) in viremic patients.
- Results corroborated previous findings using RT-PCR, highlighting sequencing's potential.
Conclusions:
- Urinary miRNA profiling can distinguish kidney transplant recipients with and without BKPV viremia.
- BKPV-specific miRNAs are promising biomarkers for monitoring viral reactivation and PyVAN pathogenesis.
- Further evaluation of sequencing for BKPV and host miRNA monitoring is warranted.
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